Bempedoic acid and its role in contemporary management of hyperlipidemia in atherosclerosis. [Review]

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Citation: Annals of Medicine. 54(1):1287-1296, 2022 12.PMID: 35533049Institution: MedStar Heart & Vascular InstituteForm of publication: Journal ArticleMedline article type(s): Journal Article | Research Support, Non-U.S. Gov't | ReviewSubject headings: *Atherosclerosis | *Hydroxymethylglutaryl-CoA Reductase Inhibitors | *Hyperlipidemias | Atherosclerosis/dt [Drug Therapy] | Cholesterol, LDL | Dicarboxylic Acids | Ezetimibe/tu [Therapeutic Use] | Fatty Acids | Humans | Hydroxymethylglutaryl-CoA Reductase Inhibitors/tu [Therapeutic Use] | Hyperlipidemias/ci [Chemically Induced] | Hyperlipidemias/dt [Drug Therapy] | Hypolipidemic Agents/ae [Adverse Effects]Year: 2022ISSN:
  • 0785-3890
Name of journal: Annals of medicineAbstract: Atherosclerotic heart disease is the leading cause of mortality and morbidity in the USA. Low density lipoprotein (LDL) has been the target for many hypolipidemic agents to modify atherosclerotic risk. Bempedoic acid is a novel hypolipidemic drug that inhibits the enzymatic activity of ATP citrate lyase in the cholesterol synthesis pathway. CLEAR Harmony, CLEAR Wisdom, CLEAR Tranquillity and CLEAR Serenity have shown safety and efficacy associated with long term administration of this drug. Studies have shown effectiveness in reducing LDL-C in both statin intolerant patients and in patients on maximally tolerated doses of statin. The fixed drug combination of bempedoic acid and ezetimibe in a recent phase III showed significant reduction in LDL compared with placebo, which might be a promising future for LDL reduction among statin intolerant patients. Bempedoic acid also reduced inflammatory markers like hs-CRP. Given these results, bempedoic acid alone and in combination with ezetimibe received the USA FDA approval for adults with heterozygous familial hypercholesterolaemia or established atherosclerotic cardiovascular disease. We present a comprehensive review exploring the underlying mechanism, pre-clinical studies, and clinical trials of bempedoic acid and discuss the potential future role of the drug in treating hyperlipidaemia.All authors: Aronow WS, Bandyopadhyay D, Devanabanda AR, Ghosh RK, Gupta M, Mamas M, Ray KK, Tummala RFiscal year: FY2022Digital Object Identifier: Date added to catalog: 2022-07-06
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Journal Article MedStar Authors Catalog Article 35533049 Available 35533049

Atherosclerotic heart disease is the leading cause of mortality and morbidity in the USA. Low density lipoprotein (LDL) has been the target for many hypolipidemic agents to modify atherosclerotic risk. Bempedoic acid is a novel hypolipidemic drug that inhibits the enzymatic activity of ATP citrate lyase in the cholesterol synthesis pathway. CLEAR Harmony, CLEAR Wisdom, CLEAR Tranquillity and CLEAR Serenity have shown safety and efficacy associated with long term administration of this drug. Studies have shown effectiveness in reducing LDL-C in both statin intolerant patients and in patients on maximally tolerated doses of statin. The fixed drug combination of bempedoic acid and ezetimibe in a recent phase III showed significant reduction in LDL compared with placebo, which might be a promising future for LDL reduction among statin intolerant patients. Bempedoic acid also reduced inflammatory markers like hs-CRP. Given these results, bempedoic acid alone and in combination with ezetimibe received the USA FDA approval for adults with heterozygous familial hypercholesterolaemia or established atherosclerotic cardiovascular disease. We present a comprehensive review exploring the underlying mechanism, pre-clinical studies, and clinical trials of bempedoic acid and discuss the potential future role of the drug in treating hyperlipidaemia.

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